COPI Complex Is a Regulator of Lipid Homeostasis

By Mathias Beller, C. Sztalryd, Noel Southall, Ming Bell, H. Jäckle, D. Auld, B. Oliver. PLoS Biology, 2008

875 citations recorded by the source corpus.

Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis. Although little is known about lipid droplet formation and regulation, it is clear that members of the PAT (perilipin, adipocyte differentiation related protein, tail interacting protein of 47 kDa) protein family coat the droplet surface and mediate interactions with lipases that remobilize the stored lipids. We identified key Drosophila candidate genes for lipid droplet regulation by RNA interference (RNAi) screening with an image segmentation-based optical read-out system, and show that these regulatory functions are conserved in the mouse. Those include the vesicle-mediated Coat Protein Complex I (COPI) transport complex, which is required for limiting lipid storage. We found that COPI components regulate the PAT protein composition at the lipid droplet surface, and promote the association of adipocyte triglyceride lipase (ATGL) with the lipid droplet surface to mediate lipolysis. Two compounds known to inhibit COPI function, Exo1 and Brefeldin A, phenocopy COPI knockdowns. Furthermore, RNAi inhibition of ATGL and simultaneous drug treatment indicate that COPI and ATGL function in the same pathway. These data indicate that the COPI complex is an evolutionarily conserved regulator of lipid homeostasis, and highlight an interaction between vesicle transport systems and lipid droplets.

Subfields: Biochemistry, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/07af6559af5c9af43759b45bb4e060aa72131bd6

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In Molecular Biology

1. Paul A Hohenlohe
2. M. Bell
3. F. Volckaert
4. E. Selker
5. M. Whitlock
6. B. Hellemans
7. B. Matthews
8. A. Hendry

In Plant Science

1. M. Whitlock
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3. J. Stinchcombe
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• Combining population genomics and quantitative genetics: finding the genes underlying ecologically important traits (2008, background): “Do ecologically similar environments favor the same genes (Calboli et al., 2003; Colosimo et al., 2004, 2005; Protas et al., 2006), or is it possible to achieve a similar phenotype with different genetic mechanisms (Hoekstra and Nachman, 2003; Hoekstra et al., 2006)?”
• Contemporary evolution, allelic recycling, and adaptive radiation of the threespine stickleback (2013, background): “Allelic recycling is clearly important to produce freshwater phenotypes influenced by ectodysplasin (Colosimo et al., 2004), Kit Ligand (Miller et al.”
• The genomic basis of adaptive evolution in threespine sticklebacks (2012, neutral): “42% (27) Probably regulatory 17% (11) Coding”
• Microsatellites and their genomic distribution, evolution, function and applications : A review with special reference to fish genetics (2006, background): “This indicates that a single gene causing a major shift in phenotype can explain cases of parallel evolution (Colosimo et al., 2004).”
• Climate change and evolution: disentangling environmental and genetic responses (2008, background): “Nevertheless, as exemplified by several recent studies in other contexts (e.g. Abzhanov et al. 2004; Colosimo et al. 2004; Shapiro et al. 2004; Abzhanov et al. 2006; Hanski & Saccheri 2006), functional polymorphisms with known ecological relevance are becoming uncovered with increasing pace.”
• Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags (2010, background): “Nonetheless, of the nine peaks we identified, the three on LG IV co-occur with previously identified QTL and specific genes [78,79,93,97,99].”
• Rapid SNP Discovery and Genetic Mapping Using Sequenced RAD Markers (2008, background): “2A, brackets) has been previously mapped to linkage group (LG) IV [15,16] and fine-mapped in some populations to the Eda locus [17].”
• Phenotypic divergence and reproductive isolation between sympatric forms of Japanese threespine sticklebacks (2007, background): “Although body size in threespine sticklebacks is greatly influenced by rearing environment (Mori & Nagoshi, 1987; Wootton, 1994; McKinnon et al., 2004), there is also a heritable component to variation in body size (McPhail, 1977; Snyder & Dingle, 1989, 1990; Snyder, 1991; Colosimo et al., 2004).”
• THE GENETIC ARCHITECTURE OF ADAPTATION UNDER MIGRATION–SELECTION BALANCE (2011, background): “…(Orr 2001; Slate 2005), with some traits defined by only a few QTL of large effect (e.g., pelvic girdle [Shapiro et al. 2004] and armor plating [Colosimo et al. 2004] in sticklebacks; flower architecture in Mimulus spp. [Bradshaw et al. 1995, 1998]; coloration in beach mice [Steiner et al.…”
• Stickleback research: the now and the next (2013, background): “QTL studies have elucidated the genetic basis of a number of divergent traits (e.g. Peichel et al., 2001; Colosimo et al., 2004; Cresko et al., 2004; Shapiro et al., 2004; Kimmel et al., 2005; Coyle et al., 2007; Miller et al., 2007a; Albert et al., 2008; Greenwood et al., 2011; Malek et al., 2012;…”
• Rapid and cost-effective polymorphism identification and genotyping using restriction site associated DNA (RAD) markers. (2007, neutral): “4B; Colosimo et al. 2004, 2005; Cresko et al. 2004).”